The smoking route is an efficient means of drug delivery. Numerous drugs of abuse are administered by this route including cocaine, marijuana, phencyclidine, heroin and methamphetamine. Methods were developed to study the pharmacokinetics and pharmacodynamics of smoked cocaine and heroin in human volunteer subjects. Healthy subjects with a recent history of abuse of the drug of interest by the smoking route participated in the studies. Following informed consent, the subjects smoked a low dose of the drug under controlled conditions to assess safety of the procedures. The subjects then participated in a double blind, placebo controlled study of smoked versus intravenous administration of drug. Behavioral and physiological measures and biological samples were collected over time. These data provide important information to our understanding of the pharmacologic actions of these drugs by the smoking route.